| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Schizophrenia is a lifelong disabling psychiatric disorder with a reported worldwide prevalence of about 1%. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001064 |
| E.1.2 | Term | Acute schizophrenia |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the long-term safety, tolerability, and pharmacokinetics of cariprazine in patients with schizophrenia |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written (signed or thumbprinted) informed consent obtained from the patient before the initiation of any study specific procedures
2. Written (signed or thumbprinted) informed consent obtained from the caregiver before the initiation of any study-specific procedures
3. Male or female inpatient, 18 to 60 years of age, inclusive
4. Current diagnosis of schizophrenia according to DSM-IV-TR criteria (295.30 Paranoid Type, 295.10 Disorganized Type, 295.20 Catatonic Type, or 295.90 Undifferentiated Type) as determined by the Structured Clinical Interview for DSM IV (new patients only)
5. Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (new patients only)
6. Completion of the double-blind treatment period in one of the lead-in studies (RGH MD-04 or RGH-MD-05) (except new patients)
7. PANSS positive syndrome subscale total score (PANSS items P1 to P7) ≤ 25
8. CGI-S score ≤ 3
9. Patients who are eligible to continue as outpatients in the opinion of the Principal Investigator
10. Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test (applies to female patients of childbearing potential only)
11. Normal physical examination findings, vital signs, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal results that are judged not clinically significant by the PI and documented as such in the eCRF
12. Body mass index between 18 and 40 kg/m2, inclusive
13. A designated caregiver who will accompany the patient at each visit (If a caregiver cannot attend a visit, written documentation from the caregiver of the patient’s study medication compliance will need to be provided.)
14. Patients must be able to speak and understand the local language sufficiently to understand the nature of the study
15. Caregivers must be able to speak and understand the local language sufficiently to understand the nature of the study
|
|
| E.4 | Principal exclusion criteria |
1. Currently meeting DSM-IV-TR criteria for any of the following:
• Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders
• Bipolar I and II disorder
• Pervasive developmental disorder, mental retardation, delirium, dementia, amnestic and other cognitive disorders
• Known or suspected borderline or antisocial personality disorder or other DSM IV-TR axis II disorder of sufficient severity to interfere with participation in this study
• Substance abuse or dependence (other than nicotine or caffeine) within the 3 months prior to Visit 1 of this study (new patients only)
2. Patients in their first episode of psychosis
3. Treatment-resistant schizophrenia over the last 2 years
4. Positive result from the blood alcohol test or from the urine drug screen (UDS) for any prohibited medication
5. History of intolerance or hypersensitivity to other drugs of the same class as cariprazine or to rescue medications, or any history of severe drug allergy or hypersensitivity
7. Suicide risk
8. Electroconvulsive therapy in the 3 months before Visit 1 of this study (new patients only)
9. Previous lack of response to electroconvulsive therapy
10. Treatment with a depot neuroleptic less than 1 cycle in duration before Visit 1 (new patients only)
11. Treatment with clozapine in the past 10 years (see protocol for exceptions)
12. Requiring concomitant treatment with any of the prohibited medications, supplements, or herbal products listed in protocol Appendix II (see protocol)
13. At Visit 2, requiring pharmacologic treatment for the control of EPS (new patients only)
14. Patients who have extrapyramidal symptoms that are not adequately controlled by anti-EPS medications in the opinion of the PI at Visit 1 (RGH-MD-04 or RGH-MD-05 completers only)
15. Patients who in the opinion of the PI, are experiencing ongoing, uncontrolled, clinically significant adverse events at Visit 1 (RGH-MD-04 or RGH-MD-05 completers only)
16. Prior participation in any investigational study of RGH-188 (cariprazine), except for patients who participated in RGH-MD-04 or RGH-MD-05
17. Women who meet the following criteria:
• Pregnant, breastfeeding, and/or planning to become pregnant and/or breastfeed during the study
• Not at least 2 years postmenopausal, surgically sterile, or practicing a reliable method of contraception that will continue for the duration of the study.
19. Any cardiovascular disease that is clinically significant, unstable, or decompensated. Other excluding conditions are detailed in the protocol.
20. Hypo- or hyperthyroidism, unless stabilized
21. Abnormally low level of vitamin B-12 or folate or psychiatric symptoms possibly secondary to any other organic medical condition
23. History of seizure disorder, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes the patient toward a risk for seizure
24. Known history of cataracts or presence of any of the following Lens Opacities Classification System III (LOCS III) findings at the screening examination:
• Nuclear opalescence (LOCS III NO) > 4
• Nuclear color (LOCS III NC) > 4
• Cortical cataract (LOCS III C) > 3
• Posterior subcapsular cataract (LOCS III P) > 0.5
25. Patients who meet any of the following LOCS III assessment criteria:
• History of intraocular surgery or laser treatment
• History or current findings of ocular disease (open- or narrow-angle glaucoma, retinopathies, corneal diseases)
• Allergies to dilating drops, optic medications, or topical ocular anesthetics that are to be used in the ophthalmologic examination
• Active bacterial or viral ocular infection
• History of clinically significant ocular trauma or complications of ocular trauma
• History of amiodarone or systemic corticosteroid use for ≥ 3 consecutive months in the past year
• Intraocular pressure of > 21 mm Hg in either eye
• Uncontrolled diabetes and/or uncontrolled systemic arterial hypertension
• Unable to dilate pupil to at least 6 mm in either eye
26. Known human immunodeficiency virus infection
27. Known history of hepatitis C infection (see protocol for exceptions)
28. Positive test for hepatitis B surface antigen and/or hepatitis B core antibody immunoglobulin M
29. Liver enzyme test results (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) > 2 × the upper limit of normal
30. Liver enzyme test results (AST and/or ALT) > 1.5 × the upper limit of normal in patients who have also tested positive for hepatitis A virus immunoglobulin M
31. History of tardive dyskinesia (except for mild cases attributed to use of conventional agents), serotonin syndrome, or neuroleptic malignant syndrome
32. History of syndrome of inappropriate antidiuretic hormone secretion
33. Treatment with any IMP within the 6 months (or at least 5 half-lives, whichever is longer) before Visit 1 (new patients only) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last Patient, Last Visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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